We plan to evaluate a clinically distinct inherited form of male pseudohermaphroditism in a large group of individuals from a small village in the Dominican Republic. We will also evaluate sporadic and familial cases which appear to have the same clinical condition. By using in vitro and in vivo techniques to study testosterone metabolism we propose to test the hypothesis that the abnormality of sexual differentiation and development is the result of decreased production of dihydrotestosterone due to a deficiency in steroid delta 4 # 5 alpha reductase activity. Investigation of the mode of inheritance of the enzyme defect through extensive pedigree studies, as well as studies of steroid metabolism to identify the carriers will also be carried out. Upon identification of the heterozygotes, genetic counseling will be possible. Evaluation of the response to administered 5 alpha dihydrotestosterone in the post-pubertal effected males will be done to elucidate the actions of dihydrotestosterone in puberty - and in particular to initiate beard growth. Finally, careful psychosexual evaluation of the affected males will be performed in order to understand their ability to change gender identity at the time of puberty. BIBLIOGRAPHIC REFERENCES: Imperato-McGinley, J., Guerrero, L., Gautier, T., and Peterson, R.E.: Steroid 5 alpha-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism. Science 186:1213, 1974. Imperato-McGinley, J., Guerrero, L., Gautier, T., and Peterson, R.E.: Steroid 5 alpha-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism. Birth Defects: Original Article Series 4:91-103, 1975.